The purpose of this study is to extend the NHLBI Twin study of the etiology of individual differences in cardiovascular disease. The proposed study will be a longitudinal follow-up 30 years after the first in-person examination done on these twins. Currently there are three waves of follow-up to the original assessment (years 10, 16, and 25), including two waves of in-person neuropsychological testing, an assessment of brain MR volumes, and a plethora of other variables to use in analyses. The proposed additional wave of testing will allow for an investigation of the contributions of genetic and environmental influences on individual differences in brain morphology (including changes in brain volumes, CSF, and white-matter hyperintensities), in cognitive functioning (including tests of verbal and visual memory, visuospatial processing and cognitive flexibility), in physical functioning (including performance-based measures of lower-extremity function) and in cardiovascular and physical health. The specific issues addressed by this study include: 1) the extent to which genetic and environmental factors contribute to continuity or change in brain structure and function in later life (e.g., do MR infarcts or large amounts of white-matter hyperintensity (WMH) lesions affect twins' progress to clinical disease?); 2) identifying which vascular and nonvascular risk factors predict progression of brain aging as measured by reductions in brain volume, increase in WMHs, decrease in frontal brain volume, and decline in cognitive and physical functioning; 3) assessing whether cognitive decline continues to be associated with changes in brain structure, and the extent to which these relationships reflect overlapping genetic influences, the cumulative effect of individual environmental influences, or a combination of both; and, 4) identifying the role that the ApoE4 allele plays in both cardiovascular disease and cognitive decline.